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Created Augmented pred/ipred plots with `augPred()`

Source: vignettes/articles/create-augPred.Rmd
create-augPred.Rmd

This is a simple process to create individual predictions augmented with more observations than was modeled. This allows smoother plots and a better examination of the observed concentrations for an individual and population.

Step 1: Convert the NONMEM model to rxode2: 

library(babelmixr2)
#> Loading required package: nlmixr2
#> Loading required package: nlmixr2data
library(nonmem2rx)

# First we need the location of the nonmem control stream Since we are running an example, we will use one of the built-in examples in `nonmem2rx`
ctlFile <- system.file("mods/cpt/runODE032.ctl", package="nonmem2rx")
# You can use a control stream or other file. With the development
# version of `babelmixr2`, you can simply point to the listing file

mod <- nonmem2rx(ctlFile, lst=".res", save=FALSE)
#> ℹ getting information from  '/home/runner/work/_temp/Library/nonmem2rx/mods/cpt/runODE032.ctl'
#> ℹ reading in xml file
#> ℹ done
#> ℹ reading in ext file
#> ℹ done
#> ℹ reading in phi file
#> ℹ done
#> ℹ reading in lst file
#> ℹ abbreviated list parsing
#> ℹ done
#> ℹ done
#> ℹ splitting control stream by records
#> ℹ done
#> ℹ Processing record $INPUT
#> ℹ Processing record $MODEL
#> ℹ Processing record $gTHETA
#> ℹ Processing record $OMEGA
#> ℹ Processing record $SIGMA
#> ℹ Processing record $PROBLEM
#> ℹ Processing record $DATA
#> ℹ Processing record $SUBROUTINES
#> ℹ Processing record $PK
#> ℹ Processing record $DES
#> ℹ Processing record $ERROR
#> ℹ Processing record $ESTIMATION
#> ℹ Ignore record $ESTIMATION
#> ℹ Processing record $COVARIANCE
#> ℹ Ignore record $COVARIANCE
#> ℹ Processing record $TABLE
#> ℹ change initial estimate of `theta1` to `1.37034036528946`
#> ℹ change initial estimate of `theta2` to `4.19814911033061`
#> ℹ change initial estimate of `theta3` to `1.38003493562413`
#> ℹ change initial estimate of `theta4` to `3.87657341967489`
#> ℹ change initial estimate of `theta5` to `0.196446108190896`
#> ℹ change initial estimate of `eta1` to `0.101251418415006`
#> ℹ change initial estimate of `eta2` to `0.0993872449483344`
#> ℹ change initial estimate of `eta3` to `0.101302674763154`
#> ℹ change initial estimate of `eta4` to `0.0730497519364148`
#> ℹ read in nonmem input data (for model validation): /home/runner/work/_temp/Library/nonmem2rx/mods/cpt/Bolus_2CPT.csv
#> ℹ ignoring lines that begin with a letter (IGNORE=@)'
#> ℹ applying names specified by $INPUT
#> ℹ subsetting accept/ignore filters code: .data[-which((.data$SD == 0)),]
#> ℹ done
#> using C compiler: ‘gcc (Ubuntu 11.4.0-1ubuntu1~22.04) 11.4.0’
#> ℹ read in nonmem IPRED data (for model validation): /home/runner/work/_temp/Library/nonmem2rx/mods/cpt/runODE032.csv
#> ℹ done
#> ℹ changing most variables to lower case
#> ℹ done
#> ℹ replace theta names
#> ℹ done
#> ℹ replace eta names
#> ℹ done (no labels)
#> ℹ renaming compartments
#> ℹ done
#> ℹ solving ipred problem
#> ℹ done
#> ℹ solving pred problem
#> ℹ done

Step 2: convert the rxode2 model to nlmixr2

In this step, you convert the model to nlmixr2 by as.nlmixr2(mod); You may need to do a little manual work to get the residual specification to match between nlmixr2 and NONMEM.

Once the residual specification is compatible with a nlmixr2 object, you can convert the model, mod, to a nlmixr2 fit object:

fit <- as.nlmixr2(mod)
#> → loading into symengine environment...
#> → pruning branches (`if`/`else`) of full model...
#> ✔ done
#> → finding duplicate expressions in EBE model...
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#> → optimizing duplicate expressions in EBE model...
#> [====|====|====|====|====|====|====|====|====|====] 0:00:00
#> → compiling EBE model...
#> using C compiler: ‘gcc (Ubuntu 11.4.0-1ubuntu1~22.04) 11.4.0’
#> ✔ done
#> rxode2 3.0.0 using 2 threads (see ?getRxThreads)
#>   no cache: create with `rxCreateCache()`
#> → Calculating residuals/tables
#> ✔ done
#> → compress origData in nlmixr2 object, save 204016
#> → compress parHistData in nlmixr2 object, save 2184

fit
#> ── nlmixr² nonmem2rx reading NONMEM ver 7.4.3 ──
#> 
#>               OBJF      AIC      BIC Log-likelihood Condition#(Cov)
#> nonmem2rx 15977.28 20185.64 20237.23      -10083.82        335.4129
#>           Condition#(Cor)
#> nonmem2rx        2.096559
#> 
#> ── Time (sec fit$time): ──
#> 
#>            setup table compress NONMEM as.nlmixr2
#> elapsed 0.041519 0.122    0.013 100.95      2.864
#> 
#> ── Population Parameters (fit$parFixed or fit$parFixedDf): ──
#> 
#>        Parameter  Est.     SE  %RSE Back-transformed(95%CI) BSV(CV%)
#> theta1    log Cl  1.37 0.0298  2.17       3.94 (3.71, 4.17)     32.6
#> theta2    log Vc   4.2 0.0295 0.703       66.6 (62.8, 70.5)     32.3
#> theta3     log Q  1.38 0.0547  3.96       3.98 (3.57, 4.42)     32.7
#> theta4    log Vp  3.88 0.0348 0.899       48.3 (45.1, 51.7)     27.5
#> RSV          RSV 0.196                                0.196         
#>        Shrink(SD)%
#> theta1      1.94% 
#> theta2      2.46% 
#> theta3      40.5% 
#> theta4      28.4% 
#> RSV               
#>  
#>   Covariance Type (fit$covMethod): nonmem2rx
#>   No correlations in between subject variability (BSV) matrix
#>   Full BSV covariance (fit$omega) or correlation (fit$omegaR; diagonals=SDs) 
#>   Distribution stats (mean/skewness/kurtosis/p-value) available in fit$shrink 
#>   Censoring (fit$censInformation): No censoring
#>   Minimization message (fit$message):  
#>     
#> 
#>  WARNINGS AND ERRORS (IF ANY) FOR PROBLEM    1
#> 
#>  (WARNING  2) NM-TRAN INFERS THAT THE DATA ARE POPULATION.
#> 
#>     
#> 0MINIMIZATION SUCCESSFUL
#>  NO. OF FUNCTION EVALUATIONS USED:      320
#>  NO. OF SIG. DIGITS IN FINAL EST.:  2.5
#> 
#>     IPRED relative difference compared to Nonmem IPRED: 0%; 95% percentile: (0%,0%); rtol=6.43e-06
#>     PRED relative difference compared to Nonmem PRED: 0%; 95% percentile: (0%,0%); rtol=6.41e-06
#>     IPRED absolute difference compared to Nonmem IPRED: 95% percentile: (2.25e-05, 0.0418); atol=0.00167
#>     PRED absolute difference compared to Nonmem PRED: 95% percentile: (1.41e-07,0.00382); atol=6.41e-06
#>     nonmem2rx model file: '/home/runner/work/_temp/Library/nonmem2rx/mods/cpt/runODE032.ctl' 
#> 
#> ── Fit Data (object fit is a modified tibble): ──
#> # A tibble: 2,280 × 27
#>   ID     TIME    DV  PRED    RES IPRED  IRES  IWRES   eta1  eta2   eta3  eta4
#>   <fct> <dbl> <dbl> <dbl>  <dbl> <dbl> <dbl>  <dbl>  <dbl> <dbl>  <dbl> <dbl>
#> 1 1      0.25 1041. 1750. -710.  1215. -175. -0.732 -0.144 0.375 0.0650 0.241
#> 2 1      0.5  1629  1700.  -70.8 1192.  437.  1.87  -0.144 0.375 0.0650 0.241
#> 3 1      0.75  878. 1651. -774.  1169. -291. -1.27  -0.144 0.375 0.0650 0.241
#> # ℹ 2,277 more rows
#> # ℹ 15 more variables: ipred <dbl>, CENTRAL <dbl>, PERI <dbl>, cl <dbl>,
#> #   v <dbl>, q <dbl>, v2 <dbl>, v1 <dbl>, scale1 <dbl>, k21 <dbl>, k12 <dbl>,
#> #   f <dbl>, rescv <dbl>, tad <dbl>, dosenum <dbl>

Step 3: Create and plot an augmented prediction 

ap <- augPred(fit)
#> using C compiler: ‘gcc (Ubuntu 11.4.0-1ubuntu1~22.04) 11.4.0’

head(ap)
#>     values        ind id   time Endpoint
#> 1 1239.488 Individual  1 0.0000  CENTRAL
#> 2 1215.358 Individual  1 0.2500  CENTRAL
#> 3 1191.924 Individual  1 0.5000  CENTRAL
#> 4 1169.164 Individual  1 0.7500  CENTRAL
#> 5 1147.057 Individual  1 1.0000  CENTRAL
#> 6 1109.689 Individual  1 1.4398  CENTRAL

plot(ap)